Elucidating the structure of Aβ(1-40) fibrils is of interest in Alzheimer's disease research because it is required for designing therapeutics that target Aβ(1-40) fibril formation at an early stage of the disease. M35 is a crucial residue because of its potential oxidation and its strong interactions across β-strands and across β-sheets in Aβ fibrils. Experimentally, data for the three-fold sy...

The growth of amyloid fibrils requires a disordered or partially unfolded protein to bind to the fibril and adapt the same conformation and alignment established by the fibril template. Since the H-bonds stabilizing the fibril are interchangeable, it is inevitable that H-bonds form between incorrect pairs of amino acids which are either incorporated into the fibril as defects or must be broken ...

abstract background and objective: highly active antiretroviral therapy (haart) can effectively prevent the progression of hiv-1 replication and increase life expectancy. there are numerous causes of treatment failure and the leading one is drug resistance. thus, we aimed to determine the hiv rt gene drug resistance mutations in patients treated with antiretroviral medications. material and met...

Amyloid fibril formation is associated with numerous neurodegenerative diseases. To elucidate the mechanism of fibril formation, the thioflavin T (ThT) fluorescence assay is widely used. ThT is a fluorescent dye that selectively binds to amyloid fibrils and exhibits fluorescence enhancement, which enables quantitative analysis of the fibril formation process. However, the detailed binding mecha...

A number of proteins can aggregate into amyloid-like fibrils. It was noted that fibril elongation has similarities to an enzymatic reaction, where monomers or oligomers would play a role of substrate and nuclei/fibrils would play a role of enzyme. The question is how similar these processes really are. We obtained experimental data on insulin amyloid-like fibril elongation at the conditions whe...

Biological screening of (hetero)aromatic compounds allowed the identification of some novel inhibitors of Abeta(1-40) aggregation, bearing indane and indole rings as common scaffolds. Molecular decoration of lead compounds led to inhibitors exhibiting a potency, measured by the Thioflavin T fluorimetric assay, ranging from high to low micromolar IC(50). The 2-(p-isopropylphenyldiazenylmethylene...

Multiscale modeling of collagen fibril is carried out by incorporating the material properties of collagen obtained from steered molecular dynamics into the finite element model of collagen fibril with inclusion of crosslinks. The results indicate that the nonbonded interactions between collagen and mineral contribute to the significant enhancement of the elastic modulus of collagen fibril at a...

Mouse prion protein PrP106-126 is a peptide corresponding to the residues 107-127 of human prion protein. It has been shown that PrP106-126 can reproduce the main neuropathological features of prionrelated transmissible spongiform encephalopathies and can form amyloid-like fibrils in vitro. The conformational characteristics of PrP106-126 fibril have been investigated by electron microscopy, CD...

Amyloid fibrils are self-assembled protein aggregates implicated in a number of human diseases. Fragmentation-dominated models for the self-assembly of amyloid fibrils have had important successes in explaining the kinetics of amyloid fibril formation but predict fibril length distributions that do not match experiments. Here we resolve this inconsistency using a combination of experimental kin...

Electron tomography is an increasingly powerful method to study the detailed architecture of macromolecular complexes or cellular structures. Applied to amyloid deposits formed in a cell culture model of systemic amyloid A amyloidosis, we could determine the structural morphology of the fibrils directly in the deposit. The deposited fibrils are arranged in different networks, and depending on t...